Background: Trial results from ML18147 and VELOUR have recently reported outcomes for BV+CT and AFLI+CT in mCRC patients previously treated with BEV. This study evaluates cost and outcomes of BV+CT vs AFLI+CT as 2L treatment for patients with mCRC who progressed after receiving a standard BEV containing regimen in the 1L setting. Methods: In the absence of head-to-head trials comparing BV+CT & AFLI+CT, an adjusted indirect comparison was conducted using the Bucher-method. Hazard ratios (HRs) from ML18147 comparing BV+CT vs CT and patients previously treated with BV in VELOUR comparing AFLI+CT vs CT were utilized. An illness-death Markov model was enhanced looking at three states (progression free, progression and death). Distributions were fit to the risks for progression (Lognormal) and mortality (Gamma) and assessed using the adjusted indirect HRs. Only direct costs were considered for patients. Costs of drugs were based on wholesale acquisition costs and costs of treating adverse events were based on Medicare reimbursement. Utilities were derived from the literature; costs and outcomes were discounted at 5%. A probabilistic sensitivity analysis (PSA) was conducted to evaluate robustness of results. Results: Results of the analysis suggest BV+CT combination is less costly compared to AFLI+CT ($39,104 less per treated patient) and similar effectiveness between BV+CT and AFLI+CT [OS 13.3 vs. 12.5 months; HR 0.94 (95% CI 0.70-1.26); 0.498 vs. 0.479 QALYs] in 2L treatment of mCRC in patients previously treated with BV. AE rates and costs were higher for the AFLI+CT arm compared to the BV+CT arm. PSA shows that BV+CT is dominant over AFLI+CT in 98% of model iterations. Increasing the efficacy of AFLI+CT by approximately 100% resulted in an incremental cost-effectiveness ratio of more than $200,000 and AFLI+CT remained dominated by BV+CT. Conclusions: Based on current available data, analysis suggest BV+CT presents lower costs and similar effectiveness outcomes than AFLI+CT in 2L treatment of mCRC in patients previously treated with BV. The higher price of AFLI and the increased rates of AEs are the primary drivers of model results.