The case study reported on acquired bevacizumab resistance in one patient receiving re-treatment with bevacizumab following radiation brain necrosis progression after bevacizumab was discontinued. This case offers novel and additional insight for bevacizumab treatment. Low-dose bevacizumab is effective for radiation brain necrosis, and radiation brain necrosis may progress after bevacizumab discontinuation, whereas too many cycles of bevacizumab treatment may induce drug-resistance and re-treatment failure following the progression. Therefore, more rational administration for radiation brain necrosis with bevacizumab may include three aspects: short-course treatment, timely discontinuation upon obtaining satisfactory effects (to prevent long-term medication associated resistance) and re-treatment after brain necrosis progression.