Background: The purpose of the study was to evaluate the efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in heavily pretreated adult patients with metastatic Ewing sarcoma. Methods: We evaluated data of the patients with metastatic Ewing sarcoma retrospectively. We recorded clinical, pathological, radiological, and treatment features of the patients and used SPSS 25. version for statistical analysis. Kaplan-Meier and Cox regression analysis were used for survival analysis. Results: Sixteen patients were included in the study. The median age was 25 (range, 20-42) years. Eleven (68.8%) of the patients were male. The origin of the tumor was bone (75%) and soft tissue (25%). The most common primary tumor localization was pelvic (41.7%), extremity (33.3%), and other sites (25%), respectively. Six (37.5%) patients were de-novo metastatic at diagnosis. The most common metastatic site was the lung (75%). Before the vincristine, irinotecan, and temozolomide (VIT) combination, patients had received at least two different chemotherapy regimens (87.5%) and palliative radiotherapy (37.5%). Median progression-free survival was 3.4 (95% CI, 1.8-4.9) months. The partial response was observed in five (31.3%) patients, and all other patients (68.7%) had progressive disease. Grade 1-2 adverse events were observed in thirteen (81.3%) patients and grade 3-4 in five (31.3%) patients. The most common adverse events were hematological (87.5%). Median overall survival was 5.6 (95% CI, 3.6-7.5) months. Conclusions: In this study, we showed real-life efficacy of vincristine, irinotecan, and temozolomide (VIT) combination in adult patients with metastatic osteosarcoma. Toxicities were concern about in these heavily pretreated patients. Treatment options of metastatic Ewing sarcoma are limited. VIT regimen may be considered in patients who have a good performance.