Background: Bevacizumab remains the dominant biologic treatment option for RAS mutant (RASmt) metastatic colorectal cancer (mCRC). While the health economic impact of bevacizumab in the RASmt subpopulation may deviate from its use in the general mCRC population, this has never been investigated. This study uses the power of real-world data to assess the cost-effectiveness of doublet chemotherapy with compared to without bevacizumab (ChemBev and ChemOnly, respectively) for first-line treatment of RASmt mCRC, while accounting for subsequent treatment in second and third line. Methods: Data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was analyzed to populate a discrete event simulation of three treatment lines, surgery of primary tumor and metastases, hospitalizations following serious adverse events, and best supportive care. Imbalance in baseline patient and disease characteristics was corrected for in all analyses using inverse probability weights. Costs were included from an Australian public payer perspective in Australian dollars (AUD). All health and economic outcomes were discounted at 5% per year. Results: Of the 507 included RASmt mCRC patients that started first-line treatment in the 2010 – 2017 time period, 345 received ChemBev and 162 ChemOnly. The corrected median time on first-line treatment was 7.1 months (95% confidence interval: 6.4 – 8.0) for ChemBev and 4.1 months (3.5 – 5.1) for ChemOnly. Time on second- and third-line treatment was comparable between the groups. Corrected overall survival was 22.6 months (21.7 – 24.0) for ChemBev and 14.3 months (12.1 – 21.7) for ChemOnly. In terms of the health economic impact, mean life years were 1.9 for ChemBev and 1.5 for ChemOnly, and mean costs were AUD 93,025 and AUD 44,929 per patient, respectively. The resulting incremental cost-effectiveness ratio (ICER) of ChemBev compared to ChemOnly was AUD 149,317 per life-year gained (LYG). Conclusions: In contrast to results from clinical trials, overall survival was substantially longer for patients who received bevacizumab, which can possibly be attributed to an imbalance between groups despite correction for known prognostic factors. At an ICER of AUD 149,317 per LYG, the economic burden of upfront treatment with bevacizumab was found to be substantial and consistent with estimates for the general mCRC population. This is mainly caused by the duration of first-line treatment, which was significantly longer for ChemBev.