Background The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) is an effective but highly toxic regimen for the treatment of advanced gastric cancer. To improve tolerability while maintaining the efficacy of the DCF regimen, we developed a modified DCF regimen including an infusional 5-fluorouracil administration according to the de Gramont regimen. Methods In this study, 70 patients with advanced gastric cancer were treated. Each 2-week cycle consisted of docetaxel (60 mg/m 2 ), cisplatin (50 mg/m 2 ), a 5-fluorouracil (400 mg/m 2 ) IV bolus, and 5-fluorouracil (2,400 mg/m 2 ) IV over 46 h plus leucovorin (400 mg/m 2 ) IV over 2 h. Results The median progression-free survival and overall survival were 9.0 months (95 % CI, 7.1–10.9) and 10.8 months (95 % CI, 7.4–14.2), respectively; the 1-year and 2-year overall survival rates were 46.3 and 18.4 %, respectively. Twenty-nine (41.4 %) partial responses, 19 (27.1 %) stable disease, and 22 (31.4 %) progression of disease were observed. Grade 3–4 toxicities included neutropenia (37.1 %), febrile neutropenia (15.7 %), thrombocytopenia (10.0 %), anemia (8.6 %), nausea and vomiting (10.0 %), stomatitis (5.7 %), infection (8.6 %), and diarrhea (2.9 %). Conclusions Our results show that a de Gramont-based DCF regimen may have tolerable toxicities and be an effective and convenient palliative treatment for advanced gastric cancer.