Background: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), represents an important component of systemic therapy for metastatic colorectal cancer (mCRC). By inhibiting angiogenesis and promoting vascular normalization, bevacizumab enhances the efficacy of cytotoxic drugs. However, despite proven benefits, some uncertainties remain regarding its safety profile, particularly the risk of gastrointestinal perforation and other vascular toxicities. Materials and Methods: This retrospective, single-center, observational study included patients with histologically confirmed mCRC treated with combination chemotherapy and bevacizumab (FOLFOX/FOLFIRI + bevacizumab) at the Oncology Department of Zemun Clinical Hospital Center between July 2022 and July 2025. Efficacy was assessed according to RECIST 1.1 criteria, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and duration of response (DoR). Adverse events were classified according to CTCAE v6.0. Results: A total of 74 patients were analyzed (56.8% male; mean age 67 ± 9 years). The median PFS was 6.5 months (IQR 3–9.8), and DoR 7.3 months (95% CI 5.2–9.5). ORR was 35.1%, and DCR 82.4%. The most common toxicities were hypertension (12.2%) and proteinuria (10.9%), while gastrointestinal perforation was observed in 4.1% of patients—slightly higher than in larger real-world series, which may be related to locally advanced disease, peritoneal carcinomatosis, or an intact primary tumor. Conclusion: Bevacizumab-based therapy demonstrated consistent efficacy and an acceptable safety profile in patients with mCRC. Although the incidence of perforation and fistula formation was somewhat higher, the therapy remained safe with careful patient selection and monitoring.

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