Background: Optimal salvage line chemotherapy for previously heavily treated advanced/ metastatic gastric cancer (AGC) is unknown, but treated with irinotecan in Japan. Ramucirumab, a human IgG-1 monoclonal antibody that targets the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. Furthermore, combination chemotherapy with ramucirumab and irinotecan based regimen (FOLFIRI) is recognized as one of the promising regimens for metastatic colorectal cancer. To date, however, use of the ramucirumab plus irinotean regimen for AGC patients has not been investigated, and recommended doses (RD) of ramucirumab plus irinotecan for patients with AGC therefore remain unknown. The aim of this study was to determine the maximum tolerated dose (MTD) and RD for systemic chemotherapy with rumucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platina and taxane. Methods: Patients received systemic chemotherapy with ramucirumab (8mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150mg/m²). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606). Results: Six patients were enrolled from August 2015 to September 2017. MTD was not reached at level 1. Irinotecan 150 mg/m² in combination with ramucirumab 8mg/kg could be administered with acceptable toxicity, and all patients were treated at these doses. No DLT was observed at Level 1. No treatment-related death was observed. Adverse events of grade 3/4 were neutropenia (17%), anemia (17%), hyponatremia (17%), hypertension (17%). Five of the six patients were evaluable for efficacy based on the RECIST criteria, and response rate and disease control rate were 20% and 100%, respectively. Conclusions: Salvage chemotherapy with a ramucirumab plus irinotecan regimen was well tolerable for patients with previously heavily treated AGC. RD was defined as ramucirumab 8 mg/kg in combination with irinotecan 150 mg/m²/day. Clinical trial information: 000018606.