Background: The randomized, phase 3 FIRE-3 trial evaluated 1L FOLFIRI + cetuximab or bevacizumab in patients with RAS wt mCRC; overall survival favored FOLFIRI + cetuximab by > 8 months. The purpose of this analysis was to evaluate the cost-effectiveness of FOLFIRI + cetuximab vs that of FOLFIRI + bevacizumab as 1L treatment for patients in Germany with RAS wt mCRC (including the patient subgroup with RAS wt, left-sided [LS] primary tumors, as LS is a predictive factor). Methods: A standard oncology 3–health-state partitioned survival cost-utility model was developed to analyze the costs and health benefits of FOLFIRI + cetuximab vs those of FOLFIRI + bevacizumab 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) gained. A 3.5% discounting rate was applied to the modeled costs and outcomes. Results: Discounted costs, health gains, and incremental cost-effectiveness ratios (ICERs) for patients with RAS wt (base case) and patients with RAS wt, LS (subgroup) mCRC 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 + cetuximab had a 64.0% and 81.6% (base case) and 80.5% and 92.4% (subgroup) probability of being cost-effective vs FOLFIRI + bevacizumab, respectively. Clinical trial information: NCT00433927Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients in Germany with RAS wt mCRC at official WTP thresholds applied by relevant European health technology assessment agencies. The cost-effectiveness of FOLFIRI + cetuximab is more pronounced in the subgroup of patients with RAS wt, LS tumors.