Background: There is no consensus on the safety and effectiveness of adjuvant chemotherapy for patients with stage III colorectal cancer (CRC) aged ≥80 years who underwent curative resection. We conducted a prospective phase II feasibility study of uracil-tegafur and leucovorin (UFT/LV) as adjuvant chemotherapy in this population. Methods: This study involved 15 institutions of the Hiroshima Surgical Oncology Study Group (HiSCO). Patients with stage III CRC aged ≥80 years who underwent curative resection with an Eastern Cooperative Oncology Group performance status of 0–1 were enrolled. Eligible patients received UFT/LV therapy (UFT, 300 mg/m² per day as tegafur; LV, 75 mg/day on days 1–28, every 35 days for five courses). Primary endpoint was feasibility, and secondary endpoints were safety and relative dose intensity. Results: Sixty-nine patients were enrolled in the study between December 2013 and June 2021. Of the 69 patients, 65 were included in the analysis, excluding two ineligible patients and two who discontinued before treatment commenced. There were 32 males and 33 females with a median age of 82 years (range, 80–88 years). There were four patients with stage IIIA CRC, 49 with stage IIIB, and 12 with stage IIIC. In the primary endpoint, administration completion rate was 67.3% (95% confidence interval: 54.9The median relative dose intensities were 84% (range, 4–100%) for UFT, and 100% (range, 4–100%) for LV. Incidence of grade three or higher adverse events were neutropenia (1.5%), aspartate transaminase elevation (3%), alanine transaminase elevation (1.5%), oral mucositis (3%), anemia (1.5%), and diarrhea (4.6%). No treatment-related deaths occurred. An independent risk factor was not identified in the background risk factor analysis for treatment discontinuation. Conclusions: Uracil-tegafur and leucovorin are not recommended as standard adjuvant therapy for patients with stage III CRC ≥80 years of age because of the possibility of lower completion rates. The frequency of serious adverse events was acceptable, and safety was confirmed in the treated patients. It is necessary to clarify the background of patients in which administration is discontinued and to investigate the impact on long-term prognosis. Clinical trial information: R000013902.