What is the best way to create a stencil for a large spray paint image?
The best first step is to convert your image into a vector format from the current raster image. Vector format images are composed of "descriptions" that could be considered as a road map of the image. As an example, a square can be defined as four points and four lines. The vector image can be easily processed by laser cutter, vinyl cutter and CNC router if you have access to these machines or are in an area with a makerspace.

If you need only one use of the image, you could have it cut in vinyl, apply it to the surface, cast your media and remove the vinyl. I suspect that it would be less expensive to have a stencil cut rather than vinyl.

A quick search for "stencil cutting services" shows me there are many resources in that respect.

If you will be creating this stencil for multi-color results, you will have to have a color separation of the vector image, with registration marks as part of the output. That is to say, you would have a set of openings on one stencil for the black, another stencil for the red.

One critical consideration is the detail and resolution of your image. The image you've posted shows dithering. This is the area where small dots appear in one color with another color as the background. This can be challenging for the cutter, if you do not perform the raster to vector conversion yourself. If you do the conversion, you will also find it challenging.

Consider how your image will appear if the dithering is removed or converted to solid colors. Will that be acceptable? Also consider to search using the terms "david bowie vector image" for a better choice of your stencil.

As an example, I found this as a result of the search:



Note that the edges are crisp and solid. Two colors means a single stencil, more easily accomplished for a reasonable price.

Another caution. This image and almost any you find will have floaters in the stencil. These are sections that have no attachment to the edge of the stencil. Stencil fonts always have the floaters secured to the edges. Art work cannot have the luxury and attain the desired result. As such, it may be necessary to resort to one-shot vinyl, as the stencil remains attached to transfer tape until applied to the surface, keeping the floaters in place until peeled from the surface. Bowie's right eye is an example if you consider that the stencil material is black and the medium is white paint. Curiously, in this example, it would appear that only his eye and nostril are floaters and the rest of the stencil is well secured by the neck area.

Some stencils can be secured by very thin strips of edited lines but have to be treated carefully in handling to avoid breaking those attachment points. In the example image, one could create a connection from the left edge of his eye to the outside and another from the right edge of the eyebrow to the right side, a thin uni-brow.

In your post, you suggest a 3' x 2' poster, which would require tiling of the stencils, I expect. You would be able to find a service that can cut the entire full size, but it might not be inexpensive.

I think the most difficult part of your project would be to find a satisfactory vector image and the remainder is simply money or labor. If you have a good vector image and good stencil material, you could print the image in tiles, cut the vector lines with a hobby knife and create it on your own.

If you create your own, you can also consider to apply spray adhesive to the tiles, attach the uncut stencil to the MDF and begin the cutting process. This also removes the problem of floating sections, as the adhesive will secure them. Some spray adhesive will release relatively easily, as will rubber cement when properly applied. MDF doesn't hold well with such adhesives, but will hold well enough for stencil cutting purposes.