Background: Medical treatment of patients (pts) with mnccRCC remains uncertain, with no established standard treatment. In addition, no data on late line of treatment have been reported. The aim of this study was to investigate clinical outcome for patients receiving 3L therapy in mnccRCC Methods: Retrospective data analysis was performed using the IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes of 3L therapy in mnccRCC pts. Kaplan Meier estimation was applied for progression-free survival (PFS) and overall survival (OS) Results: Out of all pts with mRCC treated with a targeted therapy from 2005 to 2016, 202/1027 (20%) had mnccRCC. 117 (58%) received 2L therapy and 62 (30%) received 3L therapy. These pts had papillary RCC (61%), unclassified RCC (19), Xp11translocation renal cell carcinoma (13%) and chromophobe tumors (7%). The most common 3L therapies were: everolimus (29%), sorafenib (18%), other drugs in clinical trials (16%), sunitinib (11%), axitinib (10%) and cabozantinib (10%). Baseline characteristics are displayed in Table 1. With a median follow-up of 47 months (mo) (min: 0.7 max: 74), the median PFS is 5 mo (95%CI 2.7 - 5.8) and the median OS is 11.7 mo (95%CI 10 - 20). Pts with a favourable, intermediate and poor risk International Metastatic Renal Cell Cancer Database Consortium (IMDC) score had a median OS of 21 mo (95%CI 8 – NR), 11.9 mo (95%CI 10 – 25), and 6.2 mo (95%CI 2 – 8), respectively (p < 0.0001). One patient (2%) obtained a partial response and 26 pts (51%) achieved a stable disease, among 51 evaluable pts Conclusions: This is the first report investigating the impact of 3L systemic therapy in a rare population. Selected pts could benefit of more lines of therapy and IMDC score appears to stratify well prognostic groups, especially poor risk patients.