PURPOSE: This study examined the effects of Regorafenib (Reg) on progression-free survival (PFS), overall survival (OS) and adverse events (AEs) in mCRC patients who underwent targeted treatment and chemotherapy. MATERIALS and METHODS: Patients diagnosed with mCRC who were treated between 2015 and 2023 were retrospectively examined. RESULTS: Reg was administered as a third-line treatment to 84 patients who had undergone two cycles of chemotherapy and targeted therapy and subsequently experienced progression. Treatment was initiated with a daily dose of 80 mg or 120 mg, based on the patient’s ability to tolerate the medication, and was increased to 160 mg per day. The median number of cycles prescribed for Reg treatment was four. The median PFS with Reg was 4±0.2 months, while the median overall survival (OS) was 9±1.2 months. When compared to patients who started Reg treatment at 80 mg, patients starting at 160 mg had longer median PFS and OS (PFS: 6±2.1 months vs. 4±0.2 months; p 0.05; OS: 13 ±0.7 months vs. 6±1.3 months; p = 0.069). Patients with right-sided colon cancer who received Reg as third-line therapy had a significantly longer mPFS than those with left-sided colon cancer (8 months ± 4 vs. 4 months ± 0.3, p=0.039). Patients with KRAS mutations had a prolonged mPFS than those with panRAS-wild type (6±1.6 months vs. 4±0.3 months, p=0.06). The mPFS contribution in the BRAF mutant subgroup with poor prognosis is promising, as it is similar to that of patients without BRAF mutations (4 months±0.8 x 4 months ±0.5, p=0.74). The most common AEs reported were liver enzyme elevations and dermatological toxicities. CONCLUSION: The encouraging results of positive survival contribution have been observed in subgroups of patients with poor prognosis, specifically those with KRAS or BRAF mutations, as well as those with right colon localization.