The output level from the reference buffer should be selected (ADC0REFSEL and AC0REFSEL in VREF.CTRLA) before the respective modules are enabled. The reference buffer is then automatically enabled when requested by a peripheral. Changing the reference while these modules are enabled could lead to unpredictable behavior.
The VREF module and reference voltage sources can be forced to be ON, independent of being required by a peripheral, by writing to the respective Force Enable bits (ADC0REFEN, AC0REFEN) in the Control B (VREF.CTRLB) register. This can be used to remove the reference start-up time, at the cost of increased power consumption.