Background: Randomized clinical trials have demonstrated the survival benefit provided by the addition of biologic drugs to chemotherapy (biochemotherapy) in patients with metastatic colorectal cancer (mCRC). However, Hispanic patients are underrepresented in trial populations with limited data on treatment efficacy in them. We aim to compare effectiveness of chemotherapy vs biochemotherapy among Hispanic population in the US with mCRC. Methods: This study includes two cohorts of patients: 1. age ≥ 65 years mCRC diagnosed from 2004 to 2011 who had received at least 1 dose of chemotherapy and had complete Medicare claims data using the Surveillance, Epidemiology, and End Result (SEER)–Medicare linked database, and 2. local Hispanic population from two hospitals in Bronx, New York, from 2006- 2020. Patient data were classified according to whether they received chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil or capecitabine) or biochemotherapy (bevacizumab, cetuximab, panitumumab, ramucirumab, or aflibercept, started within 3 months of chemotherapy). Overall survival (OS) was defined as the time from starting chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival. Results: A total of 188 patients with mCRC were identified. Fifty three (28.2%) received chemotherapy and 135 (71.8%) received biochemotherapy. Median ages were 69 and 68 years, respectively. There were no differences based on median income, marital status, primary site or sidedness, tumor differentiation grades or Charlson Comorbidity Score between both groups. Among patients who received only chemotherapy, 9% received second or greater lines of chemotherapy when compared to 51% in the biochemotherapy group (p <0.001). The median overall survival was 6.6 (95% CI:5.7 - 15.0) months (mo) and 15.9 (12.0 -24.5) mo, respectively. Biochemotherapy conferred an OS benefit with average HR=0.62 (0.41-0.94; p=0.023). This was most evident in the first year (HR=0.53, 0.31-0.89; 0.016), less so in 2nd year (HR=0.65, 0.28 - 1.49; 0.307) and there was an apparent reversal effect beyond 2 years (HR=1.79, 0.41-7.77; 0.436). Conclusions: In this comparative effectiveness study of a cohort of Medicare recipients and the Bronx population, with mCRC, biochemotherapy was associated with an improvement in OS, especially in the 1^st year. Patients receiving biochemotherapy are more likely to receive further lines of chemotherapy upon disease progression.