Background: FTD/TPI is approved for patients (pts) with refractory mCRC. FTD/TPI + BEV has been evaluated in refractory mCRC in phase 1 and 2 trials and shown efficacy and tolerability, but few head-to-head studies compare FTD/TPI + BEV with FTD/TPI. We therefore conducted this meta-analysis to evaluate outcomes with FTD/TPI + BEV and FTD/TPI monotherapy in mCRC. Methods: We searched MEDLINE, Embase, and Cochrane Library databases; ASCO, ESMO, and AACR proceedings (past 3 years); Clinicaltrials.gov and UMIN registries; systematic review bibliographies; gray literature; and guidelines through June 2021 for studies involving pts with mCRC treated with FTD/TPI + BEV or FTD/TPI. Only randomized controlled trials (RCTs), non-RCTs, and prospective observational studies of previously treated pts with mCRC were evaluated. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse event (AE) rates, and AE-related discontinuation rates. Fixed and random effects models based on inverse-variance weighting were used to estimate relative effects and pooled absolute outcomes for ORR, DCR, AE rates, and AE-related discontinuation rates. PFS and OS were estimated from pooled Kaplan–Meier curves using Guyot’s algorithm. Results: Twenty-nine of 875 screened publications were selected, which included a total of 10,285 pts and reported on 5 RCTs, 11 non-RCTs, and 10 prospective observational studies. In an RCT (n = 93; Pfeiffer et al. Lancet Oncol. 2020), FTD/TPI + BEV was associated with significant reductions in risks for progression and death versus FTD/TPI. Pooled efficacy outcomes were higher with FTD/TPI + BEV than FTD/TPI (Table). Pooled rates for grade ≥3 febrile neutropenia, asthenia/fatigue, diarrhea, nausea, and vomiting were similar with FTD/TPI + BEV and FTD/TPI, although grade ≥3 neutropenia occurred more frequently with FTD/TPI + BEV than FTD/TPI (43% vs 29%). AE-related discontinuation rates were similar (Table). Conclusions: This meta-analysis suggests that FTD/TPI + BEV provides benefits over FTD/TPI in pts with refractory mCRC and has a similar safety profile, but it is associated with a higher rate of grade ≥3 neutropenia. Limitations of the analysis include study design heterogeneity. Data from RCTs (eg, phase 3 SUNLIGHT trial [NCT04737187]) are required to confirm these findings.