Although resection is effective for managing resectable liver metastases from colorectal cancer, the clinical significance of chemotherapy for such metastases has remained undetermined. Therefore, we conducted a phase II trial of perioperative chemotherapy with mFOLFOX6 to examine its efficacy. A total of 41 patients were examined. The liver resection rate was the primary endpoint, whereas the response rate, adverse events, completion rate, liver injury rate, R0 resection rate, and histological results were the secondary endpoints. Overall, 34 (82.9%) patients underwent liver resection, and 77.4% and 100% had synchronous and metachronous liver metastases, respectively. The seven remaining patients did not undergo resection because of progressive disease. Moreover, 2, 15, 17, and 7 patients had a complete response, partial response, stable disease, and progressive disease, respectively, which indicated that the response rate was 41.5%. Regarding adverse events, three patients exhibited Grade 3 myelosuppression and one patient had gastrointestinal symptoms. On the basis of histopathological examination, 27, 5, and 2 patients belonged to grades 1a:1b, 2, and 3, respectively. Regarding liver injury, 29.4% had liver sinusoidal injury, whereas 11.7% had steatohepatitis. Meanwhile, all patients underwent postoperative chemotherapy. mFOLFOX6 is safe and yields favorable therapeutic effects. The indication for liver resection after a certain waiting period is clinically significant.