Purpose The addition of bevacizumab to fluorouracil-based chemotherapy is a standard of care for previously untreated metastatic colorectal cancer. Continuation of bevacizumab beyond progression is an accepted standard of care based on a 1.4-month increase in median overall survival observed in a randomized trial. No United States-based cost-effectiveness modeling analyses are currently available addressing the use of bevacizumab in metastatic colorectal cancer. Our objective was to determine the cost effectiveness of bevacizumab in the first-line setting and when continued beyond progression from the perspective of US payers. Methods We developed two Markov models to compare the cost and effectiveness of fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab in the first-line treatment and subsequent fluorouracil, leucovorin, and irinotecan with or without bevacizumab in the second-line treatment of metastatic colorectal cancer. Model robustness was addressed by univariable and probabilistic sensitivity analyses. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Results Using bevacizumab in first-line therapy provided an additional 0.10 QALYs (0.14 life-years) at a cost of £59,361. The incremental cost-effectiveness ratio was £571,240 per QALY. Continuing bevacizumab beyond progression provided an additional 0.11 QALYs (0.16 life-years) at a cost of £39,209. The incremental cost-effectiveness ratio was £364,083 per QALY. In univariable sensitivity analyses, the variables with the greatest influence on the incremental costeffectiveness ratio were bevacizumab cost, overall survival, and utility. Conclusion Bevacizumab provides minimal incremental benefit at high incremental cost per QALY in both the first- and second-line settings of metastatic colorectal cancer treatment.