We report the case of a patient with colon cancer accompanied by multiple unresectable liver metastases who showed complete response (CR) to modified TEGAFIRI (mTEGAFIRI) (tegafur-uracil/leucovorin+irinotecan) chemotherapy. The patient was a 58-year-old Japanese male with cancer of the descending colon accompanied by multiple unresectable liver metastases. Following resection of the sigmoid colon cancer, mTEGAFIRI chemotherapy was administered. Abdominal computed tomography performed upon completion of 12 courses of chemotherapy showed that the unresectable liver metastatic lesions had disappeared, indicating CR. The only adverse drug reactions (ADRs) experienced to date have been stomatitis (grade 1) and neutropenia (grade 1). Anticancer therapy has thus been continued, and CR has been maintained for 15 months. The present patient achieved CR in response to mTEGAFIRI chemotherapy, a regimen that has not previously been reported, while experiencing only mild ADRs and maintaining a good quality of life. mTEGAFIRI chemotherapy is convenient to administer and is thought to be a potentially useful treatment option for patients with unresectable, recurrent colon cancer.