Background: Tyrosine kinase inhibitors remain possible treatment options in favorable risk patients newly diagnosed with metastatic renal cell carcinoma (mRCC). In phase II study (FavorAx), axitinib showed the activity in mRCC patients with a favorable risk and history of prior VEGFR-directed therapy. Here we present the outcomes from expansion study cohort with 4 years follow-up. Methods: Patients were required to have clear-cell mRCC, favorable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. Axitinib was given orally at a starting dose of 5 mg twice daily with possible dose titration. Treatment was continued until disease progression according to RECIST version 1.1, unacceptable toxicity, death, or withdrawal of consent. All patients were assessed for efficacy. Endpoints included progression-free survival (PFS, primary); overall survival (OS), objective response rate (ORR), and safety (secondary). Results: A total of 55 patients were assessed, 58% of whom were male. Median age was 64 years. 29 (53%) patients had 2 and more metastatic sites. 73% and 27% of patients received first-line sunitinib or pazopanib. The median PFS was 19 months (95% CI, 15–23) and the median OS was 29.4 months (95% CI, 21.5–37). The 4-year OS rate was 36%. The objective response rate was 31% and 2 (3.6%) patients achieved a complete response. Disease progression was the single reason for discontinuation of axitinib. After disease progression, 62% of patients received third-line therapy. The toxicity was consistent with previously reported data. The most common adverse events associated with axitinib were hypertension, fatigue, and diarrhea, each occurring in more than 20% of patients. Conclusions: Second-line axitinib continues to show efficacy in favorable risk patients with mRCC. Long-term OS and PFS were observed with axitinib. Clinical trial information: NCT02700568.