Background: Currently, six months of perioperative or adjuvant chemotherapy (ACT) is a standard treatment option after radical surgical removal of metachronous metastases in patients with metastatic colorectal cancer (CRC). Data show that ACT improves relapse-free survival in such patients, although no difference in overall survival rate was observed. We conducted a non-randomized trial to examine the efficacy of ACT after radical resection of metachronous metastases from CRC. Methods: Patients older 18 years old and more with confirmed CRC and any site of resectable metachronous metastases were assigned to either surgery alone or adjuvant mFOLFOX6 for 6 months. The primary end point was 2-year disease-free survival (DFS). Results: Between June 2008 and September 2022, 123 patients were assigned to surgery alone group (51 patients) or ACT after surgery (72 patients). At a median follow-up of 27.0 months (20.9-33.1), 2-year DFS was 54.2% in surgery alone group versus 45.5% in ACT group. Median DFS (mDFS) was 25.5 months (95% CI 9.8 – 41.2) in surgery alone group versus 20.9 months (95% CI 13.5 – 28.4) in systemic chemotherapy (HR 0.75; 95% CI 0.45-1.25, P = 0.26). Conclusions: ACT didn’t improve DFS among patients after radical surgical resection of metachronous metastases from CRC.