We retrospectively evaluated the efficacy and safety of the modified FOLFIRI regimen in frail or elderly patients with advanced gastric cancer (AGC). We reviewed 24 frail Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or elderly (65 years or over) patients with AGC who received the modified FOLFIRI regimen as salvage chemotherapy. Patients received irinotecan 150 mg/m2 and leucovorin (LV) 100 mg/m2 as a 2 h intravenous infusion, followed by 5-fluorouracil (5-FU) 2,000 mg/m2 as a 46 h continuous infusion. Among the 24 patients, 18 (75%) had an ECOG PS of 2, and 11 (45.8%) were aged 65 years or over. A total of 113 cycles were conducted, with a median number of 4 cycles per patient. A total of 3 patients achieved partial response (PR) and 8 demonstrated stable disease (SD). On an intent-to-treat basis, the overall response rate (RR) was 12.5% and the disease control rate (PR and SD) was 45.8%. The median time to progression (TTP) was 2 months 95% confidence interval (CI), 1.9-2.1 months and the median overall survival (OS) was 5.4 months (95% CI, 4.1-6.7 months). Grade 3-4 hematological toxicities, including neutropenia, anemia and thrombocytopenia, were observed in 6 (25%), 4 (16.7%) and 1 (4.2%) patients, respectively. Additionally, 3 (12.5%) patients developed febrile neutropenia, of which 1 succumbed to pneumonia. Grade 3-4 gastrointestinal toxicities, including nausea, vomiting, diarrhea and mucositis, were observed in 3 (12.5%), 2 (8.3%), 1 (4.2%) and 1 (4.2%) patients, respectively. In conclusion, the modified FOLFIRI regimen as salvage chemotherapy for AGC patients over 65 years of age or with a poor PS was effective and acceptable. These results suggest that this regimen may be an effective option for frail or elderly patients with AGC.