I was asked to make a quick video on this so here it is. The idea is to paint or colour on a separate layer. The program is FireAlpaca but you can do this in basically every other art program that supports selection.
Bonus edit: obviously, you can also just select the area at the beginning, reverse the selection and fill it. Then paint on the locked layer. But the video is targeting the specific question about removing the colours.
This video is included in this playlist • Some more helpful videos it's pretty old and cringy but some may still find the videos on it helpful?
*This is an example of a ninja pixel: • Ninja Pixels