Background: The randomized, phase 3 FIRE-3 trial evaluated first-line (1L) FOLFIRI + cetuximab (cet) vs FOLFIRI + bevacizumab (bev) in patients (pts) with RAS wt mCRC; overall survival favored FOLFIRI + cet by > 8 months. The purpose of this analysis was to evaluate the cost-effectiveness of FOLFIRI + cet vs that of FOLFIRI + bev as 1L treatment for pts in Germany with RAS wt mCRC. Two independent subgroup analyses were conducted, one for pts with left-sided (LS), RAS wt primary tumors and another for pts with liver limited disease (LLD). Methods: A standard oncology 3–health-state partitioned survival cost-utility model was developed to analyze the costs and health effects of FOLFIRI + cet vs those of FOLFIRI + bev from a German payer perspective based on data from FIRE-3 and the literature. Health outcomes were reported in life-years (LYs) and quality-adjusted life-years (QALYs). A 3.5% discounting rate was applied to the modeled costs and outcomes. Results: Costs, effects, and incremental cost-effectiveness ratios (ICERs) for pts with RAS wt (base case), LS tumors, and LLD are summarized in the Table. Probabilistic sensitivity analyses showed that at relevant European willingness-to-pay (WTP) thresholds of €55,000 and €80,000, FOLFIRI + cet had a 64.0% and 81.6% (base case), 80.5% and 92.4% (LS tumors), and 89.9% and 93.8% (LLD) probability of being cost-effective vs FOLFIRI + bev, respectively. Conclusions: Based on our analyses, FOLFIRI + cet is cost-effective compared with FOLFIRI + bev in pts treated in Germany with RAS wt mCRC. The cost-effectiveness of FOLFIRI + cet improves for subgroups with LS tumors, or LLD.