Pat Kerrane noted that rookie Isaac Guerendo is getting consistent No. 2 reps behind Christian McCaffrey and moved him up his board. With Elijah Mitchell dealing with the usual nicks and Jordan Mason relegated to special-teams work, Guerendo’s 4.33 speed and 220-pound frame give the 49ers the explosive big-back profile Kyle Shanahan likes for spot starts. Kerrane views Guerendo as one injury away from weekly RB2 usage in the league’s most efficient rushing attack, making him a must-draft final-round stash.

Davis Mattek explained that Isaac Guerendo is the exact type of asymmetric bet you want in the back half of Best Ball Mania drafts. With Christian McCaffrey already an "extinction-event" workhorse, Guerendo either never cracks your starting lineup or instantly projects for 16-plus fantasy points the very week McCaffrey misses time. Mattek said he does not need another 11-point floor back—he already has Tyjae Spears, Jalen Warren, and Brian Robinson Jr.—so he passed on safer options like Dylan Samson for Guerendo’s nuclear upside in Kyle Shanahan’s plug-and-play rushing scheme. In his view, Guerendo is the cheapest way to buy into the NFL’s most efficient running game while still swinging for a tournament-winning spike week.

Sean Koerner pegged Isaac Guerendo as the backup to stash in San Francisco, calling him the most logical "next man up" if Christian McCaffrey’s notorious soft-tissue issues resurface. Guerendo finished 2025 with the eighth-most Best-Ball Points Added per game during the stretch he replaced McCaffrey, then tested out with the second-best athletic score at the Combine in the past 37 years. Koerner reminded listeners that Kyle Shanahan historically hands the full workload to whichever runner tops the depth chart—think Elijah Mitchell and Jordan Mason in previous seasons—making the No. 2 slot extremely valuable. The 49ers already shipped Mason elsewhere and let Elijah Mitchell walk, leaving only fifth-round rookie Jordan James and long-shot Israel Abanikanda as true competition. Koerner is monitoring camp reports, but right now he is sprinkling late-round Guerendo shares into tournament builds, betting that even 8-10 starts behind San Francisco’s zone-blocking scheme would produce league-winning spike weeks.

Sean Koerner warned best-ball drafters not to pair Isaac Guerendo with Christian McCaffrey. The rookie can only score if McCaffrey misses time, which raises the roster’s floor but destroys its ceiling by tying two roster spots to one injury-dependent outcome. Koerner wants every late-round pick to have standalone 20-point potential rather than contingent value, especially in tournament formats where first place demands spike-week production. For him, spending that pick on a back who could crack lineups alongside a healthy McCaffrey is far more profitable than locking up the 49ers’ backfield.

Greg Brainos called Isaac Guerendo a must-draft dart in the 17th–18th round range. Brainos labeled Christian McCaffrey "very high on the likely-to-get-injured list" after logging an NFL-high 339 touches last season and noted that San Francisco has the league’s most running-back-friendly scheme (4.9 yards before contact as a team). Guerendo’s 4.33 forty and 97th-percentile speed score give him true home-run juice if he inherits even half of CMC’s workload. Brainos is shocked the rookie routinely slips past pick 200 when the only backs ahead of him are a soon-to-be 28-year-old McCaffrey and journeyman Elijah Mitchell, who has missed 52% of possible games the past two years. He’s pairing Guerendo with non-CMC builds to capture asymmetric upside.

Best Ball Guy flagged rookie Isaac Guerendo as a priority flier any time he slips past ADP. He explained that he takes at least one 49ers backup every summer because Kyle Shanahan backfields routinely produce spike-week RB2s whenever injuries hit. Guerendo fits that annual thesis and, in Best Ball Guy’s words, is a "good catch-up" pick when a build needs one more running back late. Earlier in the show he pumped Jordan Mason for similar reasons, but tonight he said grabbing either Mason or Guerendo ensures exposure to whatever understudy lands the 15-touch role if Christian McCaffrey misses time.

Best Ball Guy said managers in 20-round Superflex contests should leave every draft with one of Christian McCaffrey’s backups—he specifically name-dropped rookie Isaac Guerendo and fellow depth runner Jordan James. Citing ‘injury experts,’ he noted that McCaffrey’s history of double-Achilles tendinitis boosts his re-injury probability by roughly 30 percent. Because San Francisco’s zone scheme routinely turns replacement backs into league winners, BBG sees Guerendo and James as the cheapest paths to bell-cow workloads you can find after Round 15. His approach: keep hammering elite WR and QB pockets early, then grab a 49ers insurance back as a free high-leverage chip that could deliver 20-touch weeks if CMC misses time.

Best Ball Guy said Isaac Guerendo is one of the most exciting late-round darts because he sits directly behind first-round fantasy pick Christian McCaffrey. The host stressed that when a first-round bell-cow like CMC goes down, every roster that invested early capital in him is suddenly crippled, giving Guerendo teams enormous relative leverage. Guerendo’s 4.33 forty and 220-pound frame make him a clean fit for Kyle Shanahan’s outside-zone scheme, and the rookie is already drawing praise for his pass-pro reps in OTAs—meaning he could inherit three-down usage rather than a committee. BBG likes pairing him with other contingent bets such as Braylon Allen, arguing that scooping multiple high-leverage handcuffs is the easiest way to manufacture true tournament-winning upside in Best Ball Mania rooms.

Andy Holloway said that if you roster Christian McCaffrey you should make Isaac Guerendo a priority late-round pick. Holloway pointed out that McCaffrey is already dealing with Achilles tendinitis in both legs and has a long track record of in-season nicks. Kyle Shanahan historically rides one running back when his starter is sidelined, so the McCaffrey injury scenario would almost certainly funnel every meaningful touch to Guerendo. Given McCaffrey’s first-round ADP, Andy wants the insurance locked up rather than chasing someone else’s backup on draft day.

Mattek touted rookie Isaac Guerendo as the purest contingent bet in the pool. The starter ahead of him is battling an Achilles issue; if that injury lingers, Guerendo’s speed and three-down skill set could make him the waiver-wire league-winner people chased last year with De’Von Achane.

Davis Mattek called rookie Isaac Guerendo a "huge win" any time he lasts into the double-digit rounds, especially on rosters that fade Christian McCaffrey. Guerendo ran a blazing 4.33 forty at 221 lbs, giving him the second-best speed score in this year’s class and the same athletic profile that turned Elijah Mitchell into an immediate RB1 under Kyle Shanahan. Mattek noted the 49ers gave him a $255k guaranteed contract—more than Day-3 backs Tyler Allgeier or Elijah Mitchell received—signaling intent to keep him on the 53. With CMC entering age-28 territory and already nursing a heavy workload, Mattek thinks San Francisco will spell him more than people expect, opening a path to 8-10 weekly touches and a full-workhorse scenario if McCaffrey misses time. He prefers Guerendo over veteran handcuffs like Tyler Allgeier because the rookie’s ADP still sits outside the top-200 despite genuine league-winning upside.

Davis Mattek planted his Round-13 flag on Isaac Guerendo, calling the second-year back an "S-tier" handcuff who may still log 8–10 weekly touches even behind Christian McCaffrey. Mattek thinks San Francisco’s decision to flip Jordan Mason for a late pick signals real confidence in Guerendo as RB2. The former Louisville track star ran a 4.33 forty at 221 pounds and posted an 87th-percentile burst score— traits that mesh perfectly with Kyle Shanahan’s wide-zone scheme that led the NFL in rushing EPA per play last season. Mattek expects McCaffrey’s snap share to fall from 79 % to the low-70s in an effort to keep him fresh, projecting roughly 125 carries and 25 targets for Guerendo even without an injury. Should McCaffrey miss time, historical usage shows the backup averages 19.4 fantasy points per game under Shanahan (see 2020 Jeff Wilson stretch). At a back-half-of-Round-13 ADP, Mattek believes Guerendo belongs in the same conversation as Zach Charbonnet and Trey Benson, making him a must-click in Best Ball builds.

Billy Jones called Isaac Guerendo the ideal late-round swing when drafters have already locked in premium backs. San Francisco spent Day-3 capital and guaranteed money on the 221-pound 4.33-forty rookie, a clear signal the staff views him as Christian McCaffrey’s direct understudy. Jones emphasized that any McCaffrey injury would thrust Guerendo into Kyle Shanahan’s league-best RB environment—2023 backs in that role averaged 23.4 half-PPR points per start—instantly giving teams an every-down hammer without burning additional roster spots. Because the early trio of Barkley, Taylor and McCaffrey already supplies weekly floor, Jones wants Guerendo’s asymmetric upside and said he is comfortable stopping at four total running backs once he lands the rookie.

Davis Mattek said he "doesn’t want to pass" on Isaac Guerendo in the final rounds because the rookie owns an eye-popping 9.98 Relative Athletic Score and, in Mattek’s words, is "literally the most athletic running back in the NFL right now." Mattek is unbothered by fourth-rounder Jordan James, calling James "not good" and predicting Kyle Shanahan will lean on Guerendo’s 4.33 speed for explosive change-of-pace snaps behind Christian McCaffrey. With the 49ers annually top-10 in rush EPA and known for turning raw speed backs like Raheem Mostert and Elijah Mitchell into fantasy difference-makers, Mattek views Guerendo as a high-leverage final-round bullet whose ADP will rise once training-camp clips of long runs circulate.