Background: Gastric cancer is one of the most common malignancies worldwide with a high case mortality rate. In metastatic gastric cancer, a proper combination of chemotherapy could increase the survival rate. The goal of this study is to evaluate the efficacy and safety of the combination regimen of irinotecan, oxaliplatin, and Xeloda in metastatic gastric cancer.Methods: A total of 45 patients with metastatic gastric cancer and good performance status according to the Eastern Cooperative Oncology Group (score: 0-1) received the irinotecan, oxaliplatin, and Xeloda chemotherapy regimen. Demographic data, responses to treatment, and adverse effects were gathered for all cases. Overall survival and progression-free survival rates for patients were calculated using the Kaplan-Meier estimate. Results: Patients’ mean age was 58.3 ± 11.3 years (range: 24-81). There were 73.4% male patients and 26.6% female patients. Anorexia and weight loss were the most common symptoms. Overall response rate was 50%. The majority of toxicities were anemia, nausea and vomiting (grades 1 and 2), diarrhea (grades 1 and 2), neutropenia, alopecia, and hand and foot syndrome. The one-year progression-free survival rate was 31.5 ± 7.5%, whereas the twoyear progression-free survival rate was zero. The one-year overall survival rate was 34.91 ± 8.5%. Patients had a two-year overall survival rate of 7.7 ± 6.6%. Diffuse type cancer was linked to an inferior outcome.Conclusion: Regardless of our limited number of patients, this combination could be a suitable regimen for metastatic gastric cancer in terms of low toxicity, acceptable response rate, and survival results.